The International Biodiversity Conservation Group (ICBG) program links three key issues, including human health, biodiversity conservation, and economic development by encouraging programs in the U.S. and programs in countries with high biodiversity to form integrated research teams. The ICBG described in this application involves programs located in the U.S. and Costa Rica that will cooperate to: Improve human health through the discovery of bioactive natural products from Costa Rica's rich biodiversity using ecologically-driven approaches. Contribute to the development of a bioenergy program toward discovery of cellulases and other enzymes for applications in biofuel production. Focus natural product and biosynthetic enzyme-related research on unexplored and under-explored microorganisms such as marine bacteria and insect microbial endosymbionts. Improve the research capacity and economic opportunities for Costa Rica and contribute to its National Biodiversity Strategy through gathering data for its biodiversity inventory, intensive screening of its natural products in medically relevant assays, high throughput testing of its hydrolytic enzymes, sharing of resources, clear benefit-sharing, and training of students and visiting scientists. These broad aims will be pursued through three Associate Programs located both in Costa Rica at the National Institute of Biodiversity (INBio), and the U.S. at Harvard Medical School (HMS) and the University of Michigan (U-M). The Associate Programs will conduct the pre-clinical research to discover, isolate, evaluate and develop therapeutic agents from natural products. Their collection programs, which will be coupled with genetic and phenotypic analyses, will expand Costa Rica's biodiversity inventory for microorganisms. Workshops and scientific exchanges will provide training opportunities. A bioenergy research program on sugar hydrolase discovery and commercial development is proposed as well as a program to harness enzymes from natural product biosynthesis (e.g., thioester hydrolases and decarboxylases) with application in liquid fuel production (biodiesel).